Preoperative radiotherapy in pancreatic cancer: better margins, same survival

Design

Retrospective propensity score-matched cohort, two high-volume centres

Population

452 matched patients resected for PDAC after neoadjuvant chemotherapy

Primary outcome

Event-free survival, recurrence pattern and overall survival

Effect

Overall survival HR 1.02 (0.79-1.32); R0 85.0% vs 52.2%

A retrospective cohort from two high-volume centres (JAMA Surgery, 1 October 2026) compared patients resected for pancreatic ductal adenocarcinoma after neoadjuvant FOLFIRINOX or gemcitabine/nab-paclitaxel, with or without preoperative radiotherapy. After propensity matching, 226 patients were in each group, almost all with resectable or borderline-resectable disease; median follow-up was 44 months.

Radiotherapy was associated with much better pathology: R0 resection 85.0% versus 52.2% and node-negative disease 61.5% versus 33.6%, with a small difference in complete response (6.6% vs 4.4%). Yet locoregional recurrence did not differ (subdistribution HR 0.90, 95% CI 0.53-1.54), nor did event-free survival (HR 1.10, 0.88-1.37) or overall survival (HR 1.02, 0.79-1.32). Distant recurrence was the first failure in about half of each group.

The lesson for surgeons is that a cleaner specimen is not the same as a longer life in a disease that fails systemically. Margin and node status after radiotherapy should not be read as proof that radiotherapy helped. This is observational and cannot exclude selection between groups.

The decision on preoperative radiotherapy belongs to the multidisciplinary meeting; this study gives weight to not adding it routinely in resectable and borderline disease.

• Do not use R0 or node-negative rates alone to judge whether neoadjuvant radiotherapy is working
• Discuss in the multidisciplinary meeting whether radiotherapy adds anything beyond modern chemotherapy
• Expect distant rather than local recurrence to dominate after resection
• Prioritise completing systemic therapy over adding local treatment when choices compete

Why it matters

It challenges the habit of treating margin status as a stand-in for benefit in pancreatic cancer.

Don't overread it

Observational and from two centres - it cannot show radiotherapy is useless for every patient, including locally advanced disease.

The statistics, in plain English

The survival hazard ratios sit close to 1.0 with intervals crossing it (0.79-1.32 for overall survival), so no detectable difference. Propensity matching balances what was measured, such as CA 19-9 and resectability, but not unmeasured reasons a team chose radiotherapy.

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